Metformin Promises to Extend Life for a Nickel a Pill
wired.com
wired.com
In 2014 alone, Americans filled 76.9 million
prescriptions for metformin, and some of those
prescriptions went to Barzilai himself. (He’s
been taking the drug since he was diagnosed
with prediabetes around six years ago.)
Metformin is in the biguanide class. It
works by decreasing glucose production by
the liver and increasing the insulin
sensitivity of body tissues.
The most serious potential side effect of
metformin use is lactic acidosis; this
complication is very rare, and the vast
majority of these cases seem to be related to
comorbid conditions, such as impaired liver or
kidney function, rather than to the metformin
itself.No. It could at best defer the health costs. We need to stop being passive about this and embrace the idea of (1) life extension technologies for those who want, (2) assisted suicide for those who don't.
When this philosophical shift happens we can get much more serious about life extension research and mental well-being (purpose; reasons to live) and reduce the vast expenditures on palliative care for those who are merely waiting around to die.
Anyway, I'm among the lucky 80% of those without side effects. I'm not diabetic; I take it for biohacking reasons.
Did you just say to your doctor, "Hey, doc, I'm trying to live forever here, can you hook me up with some metformin?"
I often wonder about this, when it comes to folks using drugs for off-label purposes. I know there are doctors that are amenable to prescribing things like anti-depressants on patient request, but a diabetic drug seems a harder sell.
I'm pretty sure if you are actually prescribed these for diabetes by your GP you'll pay a fraction of that cost under the NHS.
I had the same side effects, but that's ok because I'm actually T1, not T2.
But even then, metformin might help you live even longer and better. More studies needed.
And even then, these are just things to keep your body's own systems functioning optimally. I can't imagine what real anti-aging drugs might do.
The one and only reason why metformin is getting into trials is as a political lever to get the FDA to acknowledge aging as a medical condition with defined causes for which treatments will be approved. Metformin couldn't really be rejected in the way the FDA likes to reject a lot of things because it is so widely used and has been so widely used for a long time.
The future of human longevity is not tinkering with metabolism to try to push it to be a little more like calorie restricted metabolism. That is a waste of time and effort. It is enormously expensive to carry out the work to try to understand metabolism well enough to adjust it safely. Hell, look at the past 20 years of work on calorie restriction: how much has been spent, how many man-years focused on it, and the research community is still only scratching the surface on how to induce similar effects via therapies.
Yet there is another approach, one that is far more cost-effective in time and money. Repair the causes of aging. Look at removal of senescent cells: in a bare few years, and at far less cost than has been spent on calorie restriction mimetic development, researchers have demonstrated robust effects and reversal of numerous age-related conditions in mice. Unlike metformin and similar drugs, the results are consistent, sizable, and produce rejuvenation in old individuals, not just a slight slowing of aging.
There is an enormous difference between the bad way forward (typified by metformin) and the good way forward (typified by senolytics). In the former we all die on the same schedule as our parents and grandparents. In the latter we can gain decades or more of additional healthy life.
For senolytic therapies, look at Unity Biotechnology's pharmaceutical trials starting this year, Oisin Biotechnologies' gene therapy approach, SIWA Therapeutics with an antibody approach. There are a dozen or so candidate drugs worth looking at, in addition to the non-drug approaches.
If you have the connections you can order any of the various senolytic pharmaceuticals today and try them. Though this would be unwise for the chemotherapeutics with animal data, since they are not friendly compounds, and worth waiting for a year or two to see how more targeted things like FOXO4-DRI work out in human tests. A year or two from now will be a great time for self-experimentation on this front, given the range of candidates and the size of the effects in mice where there is data. Today the situation is in an awkward state where some of the easier pharmaceuticals to handle are either going to have tiny effects or have no animal data, while the others still need human data. Still, I would expect medical tourism to flourish for these things quite soon: the drugs are cheap, the beneficial effects sizable.
It's a pretty solid program all around.
(I didn't go there, but know plenty of folks that did.)
[1]: http://warddeanmd.com/articles/neuroendocrine-theory-of-agin...
[2]: http://warddeanmd.com/articles/neuroendocrine-theory-of-agin...
Gotta weigh up those risks. :)
https://tim.blog/2016/10/20/my-life-extension-pilgrimage-to-...
(i guess since this is HN the solution would be to design a statistical model that corrects for anti diabetic effect to try and demonstrate non-diabetic related anti-aging effects...)
I mean, it wouldn't directly help those of us who aren't on that path, but in terms of general societal health and average lifespan, it still seems pretty great. I like it when people don't die. It could potentially save all of us some money, too.
That said, lactic acidosis, while rare, can actually kill you. So I wouldn't take metformin without consulting a doctor.
Best punk band name EVER.
For one it makes you stupid. Obviously it interferes with everything requiring effort, from running to sex.
There are cell types in your body that will, when faced with an energy shortage simply consume themselves. Usually, this means trading a sudden death for permanent damage, for example heart muscle cells. This means that when faced with an energy shortage they will kill themselves. An overdose of Metformin can cause this to occur on a large scale and when that happens, your life is somewhere between over and very short.
Do not take any medication without being aware of the side effects and getting advice from a doctor (and let me spoil the surprise: your doctor will advise against both metformin and calorie restriction. He will be happy to prescribe you a placebo. You would be surprised how calming taking one can be)
There are other treatments that extend life, like taking aspirin daily, and other metabolism blockers, anti inflammatories and blood thinners. All come at a serious cost (DO NOT take aspirin daily unless you're happy to bleed to death with any major injury) which makes a lot of sense if you think about it.
Fasting (one way to alter insulin sensitivity without drugs) has been reported to increase focus and energy. I have been doing intermittent fasting (16 hour fast/8 hour feast, with an occasional 24 hour fast) for the past four or five months (I started logging my results about 3 months ago, but I started before that in an imprecise sort of way). I haven't noticed a significant change either way. I feel fine, with normal levels of energy and the like. I don't think I'm stupider because of it, though I probably ought to do some A/B testing to be sure.
I've never taken metformin, and haven't done any real research beyond reading the article and the Wikipedia page about it, so I don't really know what it does to someone, but as I understand it sounds like your main concern is the effect on insulin sensitivity. But, insulin sensitivity seems to be a major factor in weight and health, and growing evidence suggests that actions improving it also improve general health.
I'm not saying you're wrong, just that I don't think it's reasonable to dismiss it or to assume the most simplistic explanation of how the body works (e.g. glucose makes brains smarter, or glucose makes bodies energetic) is the correct or complete one.
Just curious about fasting, need to get into it.
My intermittent fasting looks like this:
For eight hours from midday until evening (the exact times shift a little based on my waking and sleeping schedule; 2PM to 10PM is a pretty common schedule for me), I eat like a responsible adult. Minimal junk food, desserts in moderation, try to make my meals balanced, don't eat too much sugar or simple carbs. I don't deny myself anything I crave, generally speaking, but I try not to eat garbage. I am also a vegetarian, occasional vegan, but I've been doing that for 23 years...it is unrelated to my current diet and fasting.
During the other 16 hours of the day, I eat nothing and drink nothing with calories. I drink water and unsweetened green tea (iced or hot depending on the weather; right now, it's summer and I'm in Texas, so it's iced tea). I don't drink coffee, but I normally don't drink coffee so that's not a change. Some people who fast drink coffee without sugar or dairy; I assume it has no or very few calories.
I never stop drinking water and don't know of any evidence that supports dehydration as a beneficial practice. I'm not seeking spiritual enlightenment or going on a hunger strike, I'm trying to maintain good health as I age.
The goal of intermittent fasting (as practiced by the folks I pay attention to) is to force your body to improve insulin sensitivity and to reduce caloric intake by 20-30% without having to count calories or give up favorite foods.
I don't know if it's the optimal practice, but it seems to be working OK for me, so far. I have lost about 15 pounds (and I'd lost about 5 pounds before that on a reduced calorie diet), which averages out to a little less than a pound every week since I started. Weight loss has slowed somewhat in the past month or so. I have begun lifting weights a couple times a week, though, so that may be offsetting my weight loss with regained muscle.
You probably need to come up with a fasting schedule that works for you and fits your existing daily routine. Skipping breakfast was easiest for me, and I know I have trouble sleeping well when I'm hungry, so eating late in the day is the right schedule for me. 16/8 is a reasonable balance, for me, as well. I find it's really quite easy to maintain; I go to bed two or three hours after my evening meal and then sleep through the next eight hours of the fast. Then I've only got five or six hours to go after I wake up before eating. I sip tea through that time, and most days barely notice my hunger.
I don't know if I'll do this forever but, assuming evidence continues to mount about the benefits of caloric restriction and improved insulin sensitivity, it seems like I'll keep at it for the foreseeable future.
So if you shift your example schedule two hours back to 12PM-8PM, isn't that just saying "I don't eat breakfast any more"? Lunch at noon, dinner at 6, a snack in between meals, and dessert at 7:30 would fit all the criteria you laid out, and indeed is something I end up doing pretty frequently, just without a faddish name like "intermittent fasting".
The faddish name makes it easy to google for research on the topic. You can, of course, call it whatever you like. I'm not advocating anything, I'm just sharing what I'm doing.
That said, the name does have useful meaning and context. "Fasting" hints at the metabolic response you're trying to achieve with the practice, in a way that maybe saying "skip breakfast" doesn't. And, the word "fasting" has thousands of years of history, which can also be mined for information; it's even part of the word, "breakfast".
"Skip breakfast" leaves room for "but, I had a donut at the 10AM meeting".
Metformin is not associated with cognitive impairment in interventional trials[1]. I don't think it's my job to refute every piece of nonsense with literature citations, but it could be done.
Intelligence, not directly. But I can provide links that caloric restriction diets do (that means diets that are sufficiently strict that you lose weight no matter what weight you currently have). (And that's in adults, in children they cause total disasters)
Since this is the working mechanism of that drug, I felt it relevant to put there.
I'm not a physician, but I've heard that like many life-saving drugs, Metformin's working mechanism is not yet well understood.
It's a vast oversimplification and likely completely _wrong_ that Metformin has the same effect as calorie restriction. If that was so, logic dictates that Metformin would be effective for weight loss. It isn't.